N,N,N',N'-Tetramethylethylenediamine → HCID 86690515, compound

HRID 1182629Notes

Reaction equation

HRID 1182629 reaction equation
CN(C)CCN(C)C.[CH:9]([Mg]Cl)([CH3:11])[CH3:10].[O:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]1[O:20][CH2:21][CH2:22][C:23]#[C:24][C:25]([O:27][CH3:28])=[O:26].[NH4+].[Cl-]>O1CCCC1.[Cu](I)I>[CH3:10][CH:9]([CH3:11])[C:23]([CH2:22][CH2:21][O:20][CH:15]1[CH2:16][CH2:17][CH2:18][CH2:19][O:14]1)=[CH:24][C:25]([O:27][CH3:28])=[O:26]

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 67060114HCID 67060114, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86690515HCID 86690515, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

Freshly purchased copper iodide (CuI, approximately 1.97 g, approximately 12.2 mmol) was placed under N2 in a four-neck flask. Dry tetrahydrofuran (THF) (about 35 ml) was added, followed by N,N,N′,N′-tetramethylethylenediamine (about 2.76 ml). The mixture was stirred at room temperature until a green-yellow solution was obtained and then cooled to about −70° C., upon which a green suspension was formed. Isopropylmagnesium chloride solution (approximately 12.3 mmol; about 6.1 ml of approximately 2.0 M in tetrahydrofuran (THF) was added slowly, whereupon a green suspension became colorless then turned brown. The mixture was stirred at about −70° C. for about 1 h, then methyl 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynoate (approximately 1.3 g, approximately 6.1 mmol) dissolved in dry THF (about 5-10 ml) was added. The resultant mixture was stirred at about −70° C. for about 3 h and quickly poured into an ice-cold mixture of saturated NH4Cl and hexanes/ether, approximately 5:1. The organic layer was separated, and the aqueous layer was extracted with hexanes/ether, approximately 5:1. The combined organic extracts were thoroughly washed with saturated NH4Cl solution until no blue color was seen. The organic extract was dried and concentrated. Flash chromatography with hexanes/ethyl acetate, approximately 5:1, afforded methyl 4-methyl-3-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-2-pentenoate (approximately 1.3 g, approximately 85%) as an approximately 92:8 mixture of E and Z isomers as judged from GC-MS analysis. GC-MS (E isomer, m/z, relative intensity): 172 (2), 171 (3), 155 (32), 142 (8), 141 (6), 139 (6), 95 (17), 85 (100), 67 (16), 57 (10), 55 (11), 43 (11), 41 (16). GC-MS (Z isomer, m/z, relative intensity): 172 (4), 155 (3), 154 (8), 142 (8), 141 (2), 139 (4), 123 (6), 95 (23), 85 (100), 67 (17), 57 (10), 55 (12), 43 (11), 41 (17). 1H NMR (400 MHz, C6D6, δ): 0.86 (d, J=8.0 Hz, E isomer), 0.86 (d, J=8.0 Hz, Z isomer), 1.20-1.42 (m, 4H), 1.55-1.62 (m, 2H), 1.70-1.82 (m, 1H), 2.18-2.31 (m, 1H), 3.02-3.18 (m, 2H), 3.41 (s, OCH3), 3.67-3.73 (m, 1H), 3.81-3.88 (m, 1H), 4.04-4.11 (m, 1H), 4.39 (septet, J=8.0 Hz, H-4, Z isomer), 4.52 (t, J=4.0 Hz, OCHO, Z isomer), 4.66 (t, J=4.0 Hz, OCHO, E isomer), 5.83 (br. s, H-2, E isomer), 5.86 (br. s, H-2, Z isomer). 13C NMR (101 MHz, C6D6, δ, E isomer): 20.0, 21.7 (two carbons), 26.3, 31.4, 32.9, 37.3, 50.9, 61.9, 67.3, 98.8, 115.1, 167.2, 167.8.

Workup

  1. customwas obtained
  2. temperaturecooled to about −70° C., upon which a green suspension
  3. customwas formed
  4. stirringThe mixture was stirred at about −70° C. for about 1 h
  5. additionwas added
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with hexanes/ether, approximately 5:1
  8. washThe combined organic extracts were thoroughly washed with saturated NH4Cl solution until no blue color
  9. extractionThe organic extract
  10. customwas dried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-d47919bd618b4bb0b03cfe2ce36f2dbc
Source dataset
uspto-grants-2014_03
Patent number
US08663621B2

Reaction notes

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